In the last two decades various engineered antibody derivatives, either mono or- multispecific, either mono- or multivalent have been developed and evaluated (see e.g. Holliger, P., et al., Nature Biotech. 23 (2005) 1126-1136; Fischer, N., and Léger O., Pathobiology 74 (2007) 3-14).
US 2004/0033561 refers to the DNA and the production of monovalent monobodies by co-expression of a heavy chain and a modified heavy chain. However during expression a considerably amount of undesired homodimer is formed as by-product, which is difficult to separate from the desired heterodimeric monobodies, as the homodimer and the heterodimer have the same or similar molecular weights. WO 2007/048037 refers to monovalent IgGs which corresponds to the heterodimeric monobodies of US 2004/0033561, but which can have a tagging moiety attached to the heavy chain for easier purification of the heterodimer from the difficult-to-separate homodimeric by-product.